CHLORDECONE EXPOSURE AND PROSTATE CANCER IN THE FRENCH REGION OF MARTINIIQUE

NCT06773806 | Recruiting

• 2 other identifiers: C22-522023-A00160-45
• Study Type: observational
• Target: 3,600
• Locations: 1 country
• Sites: 2

Brief Summary

Prostate cancer is the most common male cancer in industrialized countries, including France, with over 60,000 new cases each year, and represents the third leading cause of cancer-related death in men. The only known risk factors are age, ethnic origin and family history of prostate cancer. Indeed, there are considerable ethnic disparities in prostate cancer risk, with an incidence rate 60% higher in African-American men than in European-American men (Evans 2008). Similarly, in the French West Indies, where over 90% of the population is of Afro-Caribbean origin, the incidence of prostate cancer is twice as high as in mainland France. In 2015, the annual incidence was 88.5 cases per 100,000 in mainland France (Defossez 2021), while it was 184.1 cases per 100,000 in Guadeloupe, over the period 2008-2013 (Desloumeaux 2017), and 161.1 cases per 100,000 in Martinique, over the period 2005-2014 (Joachim 2019). The incidence rates observed in the French West Indies are of the same order as those observed in Afro-Caribbean populations in the UK and African-American populations in the USA (Ben Schlomo 2008, Evans 2008). The reasons for these ethnic disparities in incidence are still poorly understood, but the role of genetic factors has been suggested. Indeed, certain genetic polymorphisms have been associated with an increased individual risk of prostate cancer in men of sub-Saharan African origin (Conti 2021; Karunamuni 2021; Marlin 2021). In addition, certain environmental factors (in the broadest sense) such as obesity, chronic inflammation, diet and certain environmental pollutants, including persistent organic pollutants (POPs) such as certain organochlorine pesticides, are also strongly suspected. Among the suspected organochlorine pesticides is chlordecone, an insecticide used in the French West Indies until 1993, strongly suspected of playing a role in the occurrence of prostate cancer, particularly in the West Indies. Indeed, the Kannari study (Dereumeaux and Saoudi 2018), supported by Santé publique France, assessed the exposure of the West Indian population (Martinique and Guadeloupe) in 2013-2014 to chlordecone and certain organochlorine compounds , measured by serum levels, and quantified the determinants of this impregnation. The results of the study show that 90% of the West Indian population is indeed exposed to chlordecone, and demonstrate that chlordecone is still present in the environment (water and soil) and in food products, despite the cessation of its use in the West Indies in 1993. To date, only one epidemiological study has explored the link between chlordecone exposure and the occurrence of prostate cancer, the Karuprostate study, a case-control study carried out between 2004 and 2007 in Guadeloupe, including 623 prostate cancer cases and 671 controls (Multigner 2010). Chlordecone exposure was measured by serum levels with an initial detection limit of 0.25 μg/L (Multigner 2010), then improved to 0.06 μg/L (Emmeville 2015). The authors highlighted a significant association between chlordecone exposure and prostate cancer, with a positive dose-response relationship (OR=1.77; 95% CI, 1.21 to 2.58 for the highest tercile). This association was more specifically observed in subjects with a family history of prostate cancer and in men who had lived in a Western country, requiring further investigation. The Karuprostate study also showed that serum levels of dichlorodiphenyldichloroethylene (DDE), the main and most stable metabolite of DDT, were significantly associated with the occurrence of CaP (Emmeville 2015). These results underline the interest of assessing, along with chlordecone, co-exposure to other persistent organic or organochlorine pollutants. Furthermore, DDE exhibits anti-androgenic effects and has been shown to repress the production of Prostatic-Specific Antigen (PSA) (target gene of the androgen receptor) by human prostate cancer cell lines (Wong 2015). The supposed effect of other organochlorines such as chlordecone on androgen receptors and thus on PSA levels could thus have important repercussions in terms of prostate cancer diagnosis. Individual screening for prostate cancer is based on serum PSA levels, followed in cases of elevated PSA (\> 3-4 ng/ml) by multiparametric Magnetic Resonance Imaging (mpMRI). A recent study showed that performing pre-biopsy mpMRI, regardless of PSA level, could lead to more men being diagnosed with clinically significant prostate cancer (Eldred-Evans 2021). Finally, there is a lack of preclinical studies to investigate the distribution of chlordecone in blood and tissues, as well as the link between chlordecone and markers of prostate cancer aggressiveness. We therefore propose a case-control study in the general population of Martinique. This study will enable us to understand the nature of the link between chlordecone and prostate cancer.

Conditions

Prostate Cancer

Keywords

Epidemiology; Case-control study; Prostate cancer; Chlordecone; Pesticides

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measure : Measure of association between chlordecone exposure and the risk of prostate cancer.

  Chlordecone exposure will be measured using several complementary methods, combining serum chlordecone assays, an assessment of chlordecone exposure based on questionnaire data (occupational, residential and dietary), and the use of job-exposure or culture-exposure matrices.

  The blood sample required for chlordecone measurement and the study questionnaire will be taken for each participant during the single inclusion visit. Analysis of the study outcomes will take place at the end of the 36 months recruitment phase.

Secondary Outcomes (4)

• Primary secondary outcome measure : Measurement of the association between exposure to chlordecone and other environmental pollutants and serum Prostate-Specific Antigen levels in cases and controls.

  From the blood sampling to the statistical analyses it will take about 36 months.

• Secondary secondary outcome measure : Number of significant cancers and aggressive cancers diagnosed on targeted mpMRI biopsies versus number of significant cancers and aggressive cancers diagnosed by systematic biopsies.

  It will take around 36 months from recovery of ISUP clinical data to statistical analysis.

• Third secondary outcome measure: Distribution of chlordecone in blood, adipose and prostate tissue. Validation of a molecular signature, previously identified in vitro, on the cases' tumour tissues.

  It will take around 36 months from blood sampling and recovery of the various prostate tissues to analysis of chlordecone distribution and validation of the molecular signature.

• Fourth secondary outcome measure : Genotyping of genetic variants from blood samples using a genome-identity chip.

  It will take at least 36 months from blood sampling to genotyping.

Study Arms (3)

Prostate cancer patients

The "prostate cancer patients" group consists of : * Adult men under 75 years of age, * who are resident in Martinique for at least 6 months * who have been newly diagnosed with histologically confirmed prostate cancer in Martinique during a given three-year period in all public and private services caring for prostate cancer patients.

Controls Group 1

The 1st control group also called "negative biopsy group" consists of : * Adult men under 75 years of age, * who are resident in Martinique for at least 6 months * who have had a negative prostate biopsy following elevated PSA (\> 2.5 ng/ml) in all public and private services in Martinique identified via urologists or pathologists, during the same given 3-year period as patients, * whose the frequency matched on age (+/- 5 years) versus patients

Controls Group 2

The second control group, also called "PSA negative group", is composed of : * Adult men under 75 years of age, * who are residing in Martinique for at least 6 months * who have had a PSA test less than or equal to the threshold value of 2.5 ng/ml, during the same 3-year period as the patients, identified by a survey institute. * whose frequency is age-matched (+/- 5 years) to patients. * with quotas defined on socio-professional category in relation to men of the same age residing in Martinique (based on INSEE data).

Eligibility Criteria

• Age: 18 Years - 75 Years
• Gender Eligibility Details: Only biological males, given the research focuses on "prostate cancer".
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study participants will be selected from the Martinican male population under the age of 80.

You may qualify if:

• To take part in this research, participants must meet the following criteria:
• Patients/cases :
• All men newly diagnosed with Prostate Cancer in Martinique during a three-year given period in all public and private services caring for patients with Prostate Cancer, identified via multidisciplinary consultation meetings.
• Male adults under 75 years of age
• Resident in Martinique for at least 6 months
• Affiliated to a social security scheme or equivalent
• Have signed a free and informed consent form
• Biopsy-negative" controls (Group 1 controls):
• All men with a negative prostate biopsy following elevated Prostate Specific Antigen (PSA) assay (\> 2.5 ng/ml) within a 3-year period in all public and private services in Martinique identified via urologists or pathologists.
• Male adults under 75 years of age
• Resident in Martinique for at least 6 months
• Frequency matched on age (+/- 5 years) to patients
• Affiliated to a social security scheme or equivalent
• Signed free and informed consent
• PSA-negative" controls (Group 2 controls):

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead
• LABERCA - Laboratoire d'Etude des Résidus et Contaminants dans les Aliments: collaborator
• Direction Générale de la Santé, France: collaborator
• National Cancer Institute, France: collaborator

Study Sites (2)

The private clinic "Clinique Saint-Paul"

Fort-de-France, 97200, Martinique

NOT YET RECRUITING

University Hospital of Martinique (CHUM)

Fort-de-France, 97261, Martinique

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

We will collect blood samples in order to create a serum bank and a DNA bank : * The serum bank for the measurement of environmental persistent organic pollutants (POPs), including chlordecone. * The DNA bank for the identification of genetic variants at risk of prostate cancer.

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Central Study Contacts

Florence MENEGAUX, MD, PhD

CONTACT

+33 1 45 59 51 53; florence.menegaux@inserm.fr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2024
• First Posted: January 14, 2025
• Study Start: April 15, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2031
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

MA (2)